A A N S / C N S S e c t i o n o n T u m o r s

Spring 1999

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Editor: Ronald E. Warnick, MD

In This Issue…2

Tumor Section in theSpotlight at the 1999

AANS Annual Meeting

4In Brief

6Membership Committee

Joins ForcesWith N://OC®

7Ask the Expert—Robert

L. Martuza, MD

8AANS AbstractReview Process

10Minutes of the

Executive CouncilMeeting

12Preuss Resident’s

Research Award Paper

13Mahaley Clinical

Research Award Paper

13Young Investigator

Award Paper

Chairman’s AddressMark Bernstein, MD

NEWSTumorTumor

The Tumor Sectionis very excited aboutour ScientificProgram at theupcoming AANSMeeting in NewOrleans which willfeature a Symposiumon a very timely andinteresting topic,Intra-operative MR.

Thanks to Ron Warnick for organizing this. Wealso are proud to be presenting awards for thebest resident laboratory research paper (PreussAward) to Sandeep Kunwar, MD; the best clinicalresearch paper by a practicing neurosurgeon(Mahaley Award) to Douglas Kondziolka, MD;the best laboratory research by a neurosurgeonwithin the first 6 years of practice (Young Investi-gator Award), to Walter Stummer, MD; and thebest translational research proposal by a practicingneurosurgeon (National Brain Tumor FoundationAward) to Adam Mamelak, MD. As well,Professor Edward Oldfield will present the FarberLecture entitled “Biological Therapy of Gliomas:Promises, Expectations, and Challenges”.

At the AANS meeting I will end my two-yearterm as Chairman of this Section. I have had thechallenge of dealing with some interesting issuesand have had the pleasure and privilege ofworking with a group of outstanding andunselfish people on the Executive Council.Special thanks to the Secretary Treasurer JoePiepmeier who has done a wonderful job, and ifthe tradition of this Section continues, Joe will bevoted in as Chairman in the spring elections. TheSection will be in excellent hands with Joe at thehelm. Congratulations also to Joe for recentlyassuming the job of new Editor-in-Chief of theJournal of Neuro-Oncology. Heartfelt thanksalso to all the members of the Section for theirsupport, inquiries, interest, and input.

Rather than listing the accomplishments of theSection over the last several years, let’s look atsome of the challenges facing us. Ever-present

and important challenges are to disseminatetimely and constantly updated information to ourmembers on clinical trials, sources of researchfunding, and multi-disciplinary discoveries anddevelopments in neuro-oncology, and a numberof our Committees are working on theseinitiatives. Another important area of workrelates to the development of evidence-basedpractice parameters on a variety of neuro-oncology problems and again, work is activelyunderway in these areas.

A most important challenge which has recentlyarisen relates to embracing our skull baseneurosurgical colleagues who recently made anarticulate and thoughtful application to form anew Skull Base Section, which the Officers of theAANS and CNS voted not to support at this time.The Executive Council of the Tumor Section hasbeen in agreement with this decision for a varietyof reasons, but it is incumbent on the Tumor andCerebrovascular Sections to represent our skullbase colleagues as well as possible and give thema voice that they feel is being heard.

New information in the neuro-oncologicalrelated basic sciences and in neuro-oncologicclinical practice, especially related to technologi-cal advances, is accruing at a mind-boggling rateand the future of our Subspecialty of Neuro-Oncology in general and of our Section inspecific is exciting indeed. The ultimate indi-vidual challenge facing all of us is to keep abreastof what’s new in our Specialty and positionourselves to bring the information to bear for thebetter of our patients. It’s an exciting time withlimitless possibilities!

I thank all the Committee Chairpersons for alltheir great work and I thank all the Tumor SectionMembers for your ongoing interest in and supportof the Section. Please let us know how we canbetter serve you. If you ever have any suggestionsor inquiries please feel free to contact the Chair-man, the Secretary-Treasurer, or any of theCommittee Chairpersons. I look forward toseeing many of you in New Orleans in April.

Mark Bernstein, MD

2 Spring 1999 n TUMOR SECTION NEWSLETTER

Monday, April 26, 1999 Breakfast Seminars 6:45–9:30 AM

104 Primitive Neuroectodermal Tumors in Child-hood: Current Management and Outcomes

Moderator: Tae Sung ParkPanelists: John Buatti, Leslie Sutton, Roberta Glick,

Joseph Petronio

118 Gene Therapy of CNS NeoplasmsModerator: Michael L.J. ApuzzoPanelists: Zvi Ram, Mitchel Berger, Julian Wu

119 Pediatric Brain TumorsModerator: Harold HoffmanPanelists: Ian Pollack, Maurice Choux, Liliana

Goumnerova, Bruce Kaufman

Monday, April 26, 1999 Scientific Sessions I-IV 2:45–5:15 PM

708 Long-term Outcomes After Meningioma Radio-surgery: The Physicians and Patients PerspectiveDouglas Kondziolka, Elad Levy, Ajay Niranjan, DavidBissonette, John C. Flickinger, L. Dade Lunsford(Discussant: Donald Wright)

717 Awake Craniotomy or Stereotactic Biopsy forBrain Tumor Results in Median Length of Stay of1 or 0 Days Respectively Mark Bernstein, MichaelD. Taylor (Discussant: Ivan Ciric)

718 Craniotomy for Tumor: Outcomes in HighVolume Versus Low Volume Hospitals HenryBrem, Donlin Long, Toby Gordon, Helen Bowman,Anthony Etzel, Gregg Burleyson, Simone Betchen(Discussant: Charles Byron Wilson)

720 Gliomas Genetically Engineered to Express aModel Antigen are Eradicated Subcutaneously andProtect Against Lethal Intracranial TumorChallenge in Rats Linda M. Liau, Steven N. Sykes,Eric R. Jensen, Jeffrey F. Miller, Donald P. Becker(Discussant: Nelson Oyesiku)

728 Intraoperative Detection of Malignant Gliomas by5-ALA-induced Protoporphyrin-IX FlorescenceWalter Stummer, Susanne Stocker, Peter A. Winkler,Hans J. Reulen (Discussant: Steve Brem)

729 The Surgical Treatment of Low Grade Gliomasin the Intraoperative MRI Claudia Martin, EbenAlexander III, Ferencz Jolesz, Peter McLaren Black(Discussant: L. Dade Lunsford)

734 Radiobiology of Stereotactic Radiosurgery inMetastases and Glioblastomas. A QuantitativeLongitudinal Analysis of its Effects on rCBF,Capillary Permeability, Vascular Volume, Extra-cellular Space, Glucose Utilization and Thallium-Uptake Peter C. Warnke, Klaus Kopitzki, BruniBaumer, Danny Fritzsche, Christoph B. Ostertag(Discussant: Douglas Kondziolka)

735 Miniaturized Skull Base Surgery for AnteriorFossa Lesions (“Band-aid” Skull Base Surgery)Hae-Dong Jho (Discussant: Ossama Al-Mefty)

739 Evaluation of Radiation Effect in GlioblastomaMultiforme Patients Treated With Boron Neu-tron Capture Therapy at Brookhaven NationalLaboratory Eric Elowitz, Jacek Capala, DouglasCohen, Jeffrey Coderre, Aidnag Diaz, Darrel Joel,Ruimei Ma, George Tyson, Arjun Chanana (Discus-sant: Jeffrey Olson)

745 Concurrent Craniotomies for Multifocal Intracra-nial Tumors Ian McCutcheon, Mick J. Perez-Cruet,Raymond Sawaya, John Steel (Discussant: Michael L.J.Apuzzo)

Tuesday, April 27, 1999 Breakfast Seminars 6:45–9:30 AM

208 Management of the Fourth Ventricle TumorsModerator: Fred EpsteinPanelists: Albert Rhoton, Jr., Rudolph Fahlbusch, Bruce

Kaufman, John Buatti

212 Low-Grade Gliomas: Current Treatment andControversies

Moderator: Michael SalcmanPanelists: Edward Laws, Mitchel Berger, Michael L.J.

Apuzzo, James Rutka

216 Functional Pituitary TumorsModerator: Martin WeissPanelists: Nelson Oyesiku, Douglas Kondziolka, Diter

Luitker, Daniel Kelly

220 Pediatric TumorsModerator: Harold HoffmanPanelists: Ian Pollack, Maurice Choux, Liliana

Goumnerova

Tumor Section in the Spotlight at the1999 AANS Annual Meeting

TUMOR SECTION NEWSLETTER n Spring 1999 3

Tuesday, April 27, 1999 Plenary Session II 9:45–11:20 AM

Moderator: Russell L. TravisCo-Moderator: Steven L. Giannotta748 Radiosurgery Can Preserve Hearing in Patients

With Intracanalicular Acoustic Tumors AjayNiranjan, L. Dade Lunsford, Douglas Kondziolka,John C. Flickinger (Discussant: Donlin M. Long)

749 The Natural History of Asymptomatic, UntreatedColloid Cysts Bruce E. Pollock, John Huston III(Discussant: William Shucart)

Tuesday, April 27, 1999 Tumor Scientific Session 2:45–5:30 PM

Special Symposium2:45–3:45 PM

Intraoperative MRI in Brain Tumor SurgeryModerators: Ronald E. Warnick, Mark BernsteinSpeakers: Mark Bernstein, Peter McL. Black, Walter

Hall, Garrett Sutherland, Ronald Warnick, C.Rainer Wirtz

Scientific Session3:45–5:10 PM

Moderator: Mark BernsteinCo-Moderator: Joseph Piepmeier807 Identification of a Putative Glioma-specific EGF-

like Growth Factor Using “Differential Immuno-Absorption” Coupled to cDNA MicroarrayHybridization Linda M. Liau, Roger Lallone, StanleyF. Nelson, Jeff M. Bronstein, Donald P. Becker

808 Correlation Between Radiation Response andGenetic Aberrations in Glioblastoma MultiformeSandeep Kunwar, Gayatry Mahapatra, Stephen Huhn,Kathleen Lamborn, Andrew Bollen, Susan Chang,Michael Prados, Burt Feuerstein

809 Modulation of Microglia Motility by Glioma Cellsin Mediated by Hepatocyte Growth Factor/Scatter Factor Behnam Badie, Jill Schartner, JessicaKlaver, Jessica Vorpahl

810 Direct Correlation in CNS Malignancy of DoseIntensity to Response Rate and Duration of Survivalin Pre-clinical and Clinical Trials Edward A. Neuwelt,Laura Remsen, Leslie McAllister, Dale Kraemer

811 Transsphenoidal Surgery for Cushing’s Disease:Outcome in Patients With Normal MRI ScanPatrick Semple, Mary Lee Vance, James Findling,Edward R. Laws, Jr

812 A Novel Strategy Using Intraaterial Cisplatin andRadiation Treatment Followed by Surgical Resec-tion for Carcinoma of the Anterior and MiddleSkull Base: Preliminary Results of a Phase IITrial Shekar Kurpad, K. Thomas Robbins, Frank D.Vrionis, Jon H. Robertson

813 Long-term Follow up in Patients Who Under-went Boron Neutron Capture Therapy in JapanYoshinobu Nakagawa, Kyonghon Pooh, KatsujiKitamura, Teruyoshi Kageji

Wednesday, April 28, 1999 Breakfast Seminars 6:45–9:30 AM

310 Third Ventricle TumorsModerator: Michael L. J. ApuzzoPanelists: Alan Cohen, Joao Lobo Antunes, Christer

Lindquist

318 Cranial Nerve Preservation in Acoustic TumorSurgery

Moderator: Steven GiannottaPanelists: Douglas Kondziolka, Stephen Haines, Bruce

Pollock, Griff Harsh

Wednesday, April 28, 1999 Scientific Sessions V-VIII 9:45–11:15 AM

755 Genetic Markers Classify AnaplasticAstrocytomas Into Prognostic Groups andExplain Age-related Survival Sandeep Kunwar,Gayatry Mohapatra, Michael Prados, BurtFeuerstein (Discussant: Mark Bernstein)

756 Chemotherapy Without Irradiation for NewlyDiagnosed CNS Germ Cell Tumors (GCTs):Long-term Follow-up and Quality of Life on anInternational Cooperative Trial Howard Weiner,Maria C. Pietanza, Casilda Balmaceda, Jonathan L.Finlay (Discussant: Bruce Kaufman)

continued on page 12

4 Spring 1999 n TUMOR SECTION NEWSLETTER

American Brain Tumor Association

Meeting the Needs of the Research CommunityThe American Brain Tumor Association (ABTA) has a proud

history of funding research and providing education andresource information to brain tumor patients and their families.Periodically, we review and evaluate our programs to determineif they adequately fulfill the needs of the research communityand our patient constituents.

Our mission is to eliminate brain tumors, provide patientservices, promote excellence in patient care, and advocate for theinvestigation of innovative research and treatment approaches.How should our funds be used to best meet our mission?

Following is a brief overview of our current programs:

Research AwardsTwo-year Postdoctoral Basic Research Fellowships One-year Translational Research Grants Medical Student Summer Fellowships Professional Meeting Support Young Investigator Grants Nursing Research Grants

Education and Awareness Patient Education Publications Printed Resource Information Social Services Symposia & Town Hall Meetings Web site North American Brain Tumor Coalition

Are there new programs we should be developing, or are thereunmet needs we should be addressing? Please send us yourinput at (847) 827-9910 or via e-mail at info@abta.org.

National Brain Tumor Foundation

Exciting Research Projects Funded by the National BrainTumor Foundation

The National Brain Tumor Foundation and Cancer Care, Inc.are sponsoring the first patient teleconference of 1999, whichwill focus on the latest brain tumor treatments. This one-hourteleconference, which will take place on Tuesday, April 27,1999, will feature Jeffrey Bruce, MD, Director of Bartoli TumorLaboratory, and Director of Neuro-Oncology at ColumbiaCancer Center. Dr. Bruce will discuss clinical trials and promis-ing new treatments.

If your patients are interested in participating, please contactNBTF at (800) 934-2873 or via e-mail at nbtf@braintumor.org.

NBTF Supports Genetic ResearchOnce again, the NBTF has been fortunate enough to provide

funding for a bevy of research projects. In keeping with ourresearch mission, we always look for projects that will movequickly from pure research to brain tumor patient applications.Also, patient quality of life studies are a high priority for ourgrant-funding program.

In October 1998, the NBTF awarded a grant to RobertJenkins, MD, of the Mayo Clinic for his project to betteridentify the chromosome 19q tumor suppressor gene. Identifi-cation of this gene can help determine which patients willbenefit from chemotherapy and which will not. The projectbuilds on the success of another NBTF-funded study conductedlast year by David Louis, MD, of Massachusetts GeneralHospital. This new research will expand upon the use of 19qgene beyond oligodendroglioma therapy.

In December 1998, NBTF also awarded a research grant toTracy Batchelor, MD, of Massachusetts General Hospital toexpand this genetic predictor research to mixed glioma tumors.

NBTF salutes all of our recent grant recipients for theirdedicated work on behalf of patients everywhere. It is ourgreatest wish that their ongoing research will greatly improvethe quality of life of patients with all types of brain tumors.

Brain Tumor Awareness Week Set For May 2-8, 1999Mark your calendars now so you can do your part to in-

crease awareness about brain tumors and promote the need formore research funding. Brain tumor patients, their familiesand friends are invited to participate in all the activitiesplanned for Brain Tumor Awareness Week, which will takeplace May 2–8, 1999.

All the member organizations of the North American BrainTumor Coalition will join together for a rally in Washington,D.C. on Tuesday, May 4, followed by a luncheon for membersof Congress. If you can come to Washington, we will train youto meet with your congressperson. This is a great way to shareyour personal story with someone who can influence braintumor research spending priorities at the National Institutes ofHealth (NIH). It’s also a good opportunity to meet yourlegislators in person!

For more information, contact Janis Brewer, NBTF ExecutiveDirector and Chair of Brain Tumor Awareness Week, at (800)934-2873.

Information in Spanish about Brain TumorsThe National Brain Tumor Foundation is currently develop-

ing patient information in Spanish and is looking for your input.If you are a health professional who works with Spanish speak-ing patients, or know of any Spanish speaking patients whowould be willing to complete a brief questionnaire, please

In Brief...

TUMOR SECTION NEWSLETTER n Spring 1999 5

Use NIH Web Site as aResource

A good step for increasing the success rate for publishedinitiatives is to search the previously funded NIH grantsthrough the CRISP database of funded applications athttp://www.nih.gov/grants/award/award.htm or through theCommunity of Science Web site at http://www.cos.com.

The AANS/CNS Section on Tumors Research Committeeis interested in input from our members. Please forwardyour suggestions and ideas to Roberta P. Glick, MD, at(312) 633-6328 or by fax at (312) 633-6494.

Neuro-Oncology FundingOpportunities

Current funding sources (and phone numbers) relevant tobrain tumor research include:

AANS Young Investigator Award (847) 692-9500American Brain Tumor Association (847) 827-9910American Cancer Society (404) 329-7612American Institute for Cancer Research (202) 328-7744Cancer Control Research Program-NIH/NCI (301) 496-8520Cancer Research Foundation of America (703) 836-4412Fogarty International Center (301) 496-1653National Brain Tumor Foundation (800) 934-2873Pfizer Postdoctoral Fellowships (800) 201-1214Sloan Basic Research Fellowships (212) 649-1649Dept. of Health and Human Services (301) 496-9248James S. McDonnell Foundation (314) 721-2532Small Business Innovative Research (301) 206-9385North American Brain Tumor Coalition which includes:

Acoustic Neuroma Association of Canada (403) 428-3384Brain Tumor Foundation of Canada (519) 642-7755National Brain Tumor Foundation (800) 934-2873The Brain Tumor Society (617) 783-9712American Brain Tumor Association (847) 827-9910Children’s Brain Tumor Foundation (212) 448-9494Pediatric Brain Tumor Foundation of the U.S. (704) 665-6891The Preuss Foundation (619) 454-0200

contact Rob Tufel, NBTF Director of Patient Services, 785Market Street, Suite 1600, San Francisco, California 94103.Phone (800) 934-2873.

Society for Neuro-Oncology

Plans for SNO Meeting UnderwayThe Society for Neuro-Oncology (SNO) will host its fourth

Annual Meeting November 18-21, 1999, in Scottsdale, Arizona.SNO was formed in 1995 to bring together all disciplinesinterested in the treatment and research of central nervous systemtumors. The deadline for abstract submission is May 15, 1999.For more information about this meeting or membership inSNO, contact Jan Esenwein at (713) 745-2344, by fax (713) 794-4999, via e-mail at esen@audumla.mdacc.tmc.edu. or visit SNO’sWeb site at www.socneuro-onc.org.

Radiation Therapy Oncology Group

RTOG Wants YouThe Radiation Therapy Oncology Group (RTOG) is actively

soliciting involvement from neurosurgeons at participatinginstitutions. The AANS/CNS Section on Tumors is workingwith the Neurosurgical Subcommittee of the RTOG to estab-lish new protocols involving both surgical and radiation therapymodalities. The RTOG hosts bi-annual meetings, at which timenew concepts and protocols are discussed. Funding is availablefor full protocol involvement, as well as the investigation ofspecific scientific questions using the clinical and researchstructure of the RTOG.

Members of the Tumor Section who are at participatinginstitutions should submit outlines of discussion or researchproposals to either Dennis Bullard, MD, or Karen Johnston,MD, for inclusion at the time of the RTOG NeurosurgicalSubcommittee Meetings. It is hoped that the Tumor Section andthe Neurosurgical Subcommittee can work together to furtherdevelop these research topics.

Please submit research proposals to:

Dennis E. Bullard, MDRaleigh Neurosurgical Clinic, Inc.3700 Barrett DriveRaleigh, NC 27609(919)-785-3400(919)-783-7778 (fax)

6 Spring 1999 n TUMOR SECTION NEWSLETTER

T he Membership Services Committee of the AANS/CNSSection on Tumors has partnered with NEUROSUR-

GERY://ON-CALL® (www.neurosurgery.org) to developInternet-based resources related to brain tumor research andtherapy. The services under development include:

(1) Expanded lists of neuro-oncology fellowships, fundingsources, and meetings of interest.

(2) Links to related Web sites.(3) An online listing of current publications that will be

updated monthly. Members will have the opportunityto view a list of new brain tumor publications andbook reviews and order textbooks of interest online.

(4) An online membership directory that will allowsearches by name, institution, or geographical loca-tion. Several unique features will be available throughthe membership directory including direct e-mail, listserve capabilities, and links to member Web sites.

(5) A national survey on negative brain tumor trials thatwill be coordinated by Tom Chen, MD, from theUniversity of California (Los Angeles).

(6) Members will have the opportunity to submit braintumor questions that will be addressed on the basis ofinformation available through the National CancerData Base. This service is to be coordinated by Herb

Membership Committee Joins Forces With N://OC®

Anthony Asher, MD

Internet Sites Pertaining to Neuro-OncologyA number of Internet resources are now available to investigators, physicians, and patients.

Some of the more recent Web sites include:

Engelhard, MD, from Northwestern University(Evanston).

(7) A listing of support resources for brain tumor patientsand their families.

(8) A multidisciplinary effort designed to provide aconcise summary of literature relevant to neuro-oncology on a quarterly basis. This particular serviceis being offered jointly with the Society for Neuro-Oncology.

(9) Tumor Section members will also have the opportu-nity to interact with members of the Society forNeuro-Oncology through links to the SNO Web site.We are particularly excited about links tomultidisciplinary online discussion groups focused onbrain tumor diagnosis and treatment.

In the near future, we will be sending all AANS/CNS Sectionon Tumor members a notice with additional informationregarding the membership directory, e-mail services, anddiscussion groups. We expect that most of these services will beavailable by the late fall. If you do not have e-mail or Internetaccess, we strongly encourage you to acquire these capabilitiessoon so that you can take advantage of these new services.

Human Genome Projecthttp://www.ornl.gov/TechResources/Human_Genome/

research.html

National Library of Medicinehttp://www.nlm.nih.gov/databases/freemedl.html

American Brain Tumor Associationhttp://www.abta.org

Brain Tumor Foundation of Canadahttp://www.btfc.org

National Brain Tumor Foundationhttp://www.braintumor.org

Pediatric Brain Tumor Foundation of the United Stateshttp://www.ride4kids.org

The Brain Tumor Societyhttp://www.tbts.org

Clinical Trials and Noteworthy Treatments forBrain Tumors

http://virtualtrials.com

PDQ Brain Tumor Trialshttp://cancernet.nci.nih.gov

American Association for Cancer Researchhttp://www.aacr.org

Physician Online Center Watchhttp://www.pol.net

Society for Neuro-Oncologyhttp://www.socneuro-onc.org

TUMOR SECTION NEWSLETTER n Spring 1999 7

F ollowing is a profile highlighting Robert L. Martuza, MD,and the novel gene therapy trials he is conducting out of

Georgetown University and the University of Alabama. This isthe first in a series of profiles that highlight the research of aprominent neurosurgeon in the medical community.

Q. Can you describe the G207 herpes mutant that is currentlyin Phase I testing at Georgetown University and theUniversity of Alabama?

A. G207 is a vector derived from a herpes simplex virus – type1 known as strain F. The G207 has deletions of both copiesof the ICP34.5 genes and an inactivating mutation of theICP6 gene (inactivated due to insertion of a lacZ gene).

Q. What features distinguish this virus from other herpesmutants?

A. Having several widely spaced deletions and mutations,reversion to wild-type is unlikely. Both the ICP34.5 andICP6 mutations lead to decreased neuropathogenicity.Moreover, the ICP6 mutation selects for viral replication ingrowing cells such as those present in a malignancy.

Q. Can you highlight some of the challenges that you encoun-tered during the FDA approval process?

A. The FDA was helpful. We had three meetings with them plusother conversations. They, like we, were concerned aboutvarious safety aspects. Indeed, they posed several questions atour early meetings that lead to further experiments to demon-strate safety. We ultimately met all questions with experimen-tal evidence and received permission to proceed.

Q. Which patients are eligible for the current Phase 1 clinical trial?

A. The inclusion criteria and exclusion criteria are extensiveas you might expect, but basically patients with recurrentmalignant glioma after radiotherapy (and chemotherapy)are eligible. This includes glioblastoma, anaplastic astrocy-toma, and gliosarcoma in adult patients with a Karnofsky of70 or more.

Q. Can you describe the protocol treatment regimen?

A. Under local anesthesia, via a burr hole, the virus is deliv-ered stereotactically into a locus in the enhancing area ofthe tumor.

Q. Was stereotactic administration chosen to allow assess-ment of tumor response?

A. In this Phase I dose escalating study of potential toxicity, wehave chosen to inoculate into the enhancing tumor. In laterstudies we are considering other inoculation strategies.

Ask the Expert—Robert L. Martuza, MDRonald Warnick, MD

Q. Can you describe the study endpoints?

A. Since this is a Phase I study, we are following patient MRIscans, clinical status and survival, as well as multiplelaboratory tests.

Q. What is the current status of the Phase I study?

A. Neurovir, Inc. is the sponsor of the Phase I study and JamesMarkert, MD, at the University of Alabama and MichaelMedlock, MD, at Georgetown University are the PrincipalInvestigators for the Phase 1 study in progress. We have entered15 patients in the study thus far and have not seen HSV-relatedtoxicity and we continue to dose escalate. Presentations of thedata will first be to the FDA and to both internal and externalreview committees and then to various meetings such as theAANS/CNS, as well as cancer and herpes virus meetings.

Q. What are your plans for a Phase II study?

A. We are currently evaluating the state of the ongoing Phase Istudy and are preliminarily planning for a possible multi-center Phase II study.

Q. Are you planning clinical trials with G207 for othertumor types?

A. Plans are being made to file for approval of HSV-therapy ofother tumors including tumors outside of the nervous system.

Q. Do you have any new viral constructs under development in thelaboratory that have promise for translation to clinical trials?

A. There are vectors that have different constructions andproperties that are expected to go into clinical trial in thenear future.

Q. Do you have any final thoughts about the prospects ofherpes gene therapy for malignant glioma?

A. I think this is a very exciting time. Thus far we have not seenearly stage toxicity and have been able to escalate several logsin the Phase I G207 trial. G207 was designed with safetyforemost in mind. However, HSV is a very large virus andcan be altered in many potentially useful ways. Having shownthe safety of G207 at high titer, for example, one may wish toconsider a more actively growing or less attenuated vector.One can also consider other routes of administration,treatment of other tumor types, and the insertion of othergenes. Recent work from our laboratory suggests that suchvectors also may be used to stimulate an antitumor immuneresponse. This and related vectors have now been studied inmany laboratories by investigators and efficacy is convincingin multiple animal tumor models. We now need to optimizethis in people. That is the real challenge.

8 Spring 1999 n TUMOR SECTION NEWSLETTER

Most AANS/CNS Tumor Section members are familiarwith the procedures for abstract submission to the AANS

Annual Meeting. However, the mechanics of the abstractselection process are largely unknown and remain somewhatmysterious. Following is a description of the abstract reviewprocess that was used for the upcoming AANS Annual Meeting.I hope it will give you a better understanding of the reviewprocess and assist you in planning future abstract submissions.

Methods for SelectionAll abstracts for the 1999 AANS Meeting were submitted

through the Online Abstract Center (NEUROSURGERY://ON-CALL®). The designated reviewers were provided a codenumber and password to allow online review and scoring of theabstracts. Tumor abstracts were individually reviewed by fivemembers of the AANS Scientific Program Committee and fivemembers of the Executive Committee of the Section on Tumors.

Abstracts were assigned a score of 1 (lowest) to 5 (highest) andseparate scores were provided for each requested presentationformat (i.e., oral and poster). Reviewers did not grade abstractswhen a conflict of interest existed (i.e., same institution). At thecompletion of the grading process, the individual scores of thefive Tumor Section reviewers were averaged to determine theTumor Section Composite Score. The final abstract score wascalculated by averaging the Tumor Section composite score (1/6 weight) with the scores of the five AANS Scientific ProgramCommittee Members (5/6 weight).

The Executive Committee of the Section on Tumors receiveda list of the top 60 tumor abstracts based on composite scores.This ranking formed the basis for selection of the AANS/CNSSection on Tumors awards including the Preuss Award (bestresident laboratory research paper), Mahaley Award (bestclinical research paper by a practicing neurosurgeon), andYoung Investigator Award (best laboratory research paper by aneurosurgeon within the first six years of practice). The AANSScientific Program Committee then selected tumor abstractsappropriate for oral presentation in the Plenary Sessions and theSection’s afternoon program, as well as poster presentations.Notification letters were generated by the National Office anddistributed a few weeks later.

Tumor Section in the SpotlightA total of 205 tumor abstracts were submitted for the 1999

AANS Annual Meeting in New Orleans. The majority ofabstracts (66 percent) were submitted for consideration as eitheroral or poster presentations, whereas the remainder specifiedoral presentation only (19 percent) or poster presentation only(15 percent).

Clinical abstracts far out-numbered basic science abstracts(79 percent vs. 21percent). Common clinical topics included:

(1) Retrospective reviews of defined patient groups (i.e., pitu-itary adenomas in children), (2) Surgical techniques, (3) Clini-copathologic or molecular correlative studies, (4) Radiation orchemotherapy approaches, and (5) Case reports. The basicscience abstracts generally focused on translational therapy(gene therapy, immunotherapy, and targeted toxins) or cellularmechanisms such as signal transduction, angiogenesis,apoptosis, and invasion.

Of the 205 submitted tumor abstracts, 168 (82 percent) wereselected for oral or poster presentation. Thirty-three abstracts(16 percent) were accepted for oral presentation and the vastmajority had a clinical focus (n=29). These selected oralpresentation abstracts fell into one of several clinical categories:(1) Phase III clinical trial results, (2) Large series of an uncom-mon clinical entity (i.e., plexus tumors), (3) Innovative surgicaltechniques, (4) Molecular prognostic factors, and (5) Highimpact medical economics. Interestingly, all four basic scienceabstracts accepted for oral presentation described uniquetranslational therapies for malignant glioma.

At the other end of the spectrum, 37 tumor abstracts wererejected (18 percent). None of the 17 abstracts reporting a singlecase study were accepted for presentation. The other unsuccess-ful abstracts were submitted for oral presentation only, but werenot competitive because of small patient numbers, lack ofinnovation, or insufficient abstract details.

What Does This Mean For You?The AANS abstract selection process is a complex, yet highly

organized series of events that receives significant input from theAANS/CNS Section on Tumors. The overall high acceptancerate (82 percent) for tumor abstracts allows for broad participa-tion by our Section members in the AANS Annual Meeting.

Because of the relatively small number of oral presentation slots(four) in the Section’s afternoon session, only the most outstandingtumor abstracts are competitive for the free papers session. TheExecutive Committee of the Section on Tumors is currentlyworking with AANS leadership to allow a greater number of shortoral presentations in the Section’s afternoon session. This willprovide greater opportunities for our Section members.

Editor’s note: It should be noted that this article only describes theAANS abstract review process and may not be directly applicable to theCNS Annual Meeting which has a different meeting format andabstract review process.

The AANS Abstract Review Process — Everything YouAlways Wanted to Know, But Were Afraid to AskRonald Warnick, MD

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Congress of Neurological Surgeons? q Yes q No

q Active q Honorary q International q Resident q Senior

Are you currently involved in active brain tumor research?

Clinical: q Yes q No Basic: q Yes q No

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Application for Membership

AANS/CNS Section on Tumors

Please send your complete application and curriculum vitae to:Michael W. McDermott, MD

University of California, San Francisco533 Parnassus Ave., U-126

San Francisco, CA 94122-2722

10 Spring 1999 n TUMOR SECTION NEWSLETTER

AANS/CNS Section of TumorsOctober 5, 1998 n Seattle, Washington

The Executive Council of the AANS/CNS Section on Tumorswas called to order at 6:30 AM by the Chairman, Mark Bernstein,MD. In attendance were Anthony Asher, MD; Mitchel Berger,MD; Peter Black, MD; William Chandler, MD; WilliamCouldwell, MD; Roberta Glick, MD; Edward Laws, MD;Timothy Mapstone, MD; Michael McDermott, MD; NelsonOyesiku, MD; Joseph Piepmeier, MD; Jack Rock, MD; JamesRutka, MD; Laligam Sekhar, MD; and Ronald Warnick, MD.

Committee Reports

Secretary/Treasurer’s ReportThe minutes from the Executive Council’s meeting on April

27, 1998 in Philadelphia, were accepted without change. Thefinancial report for the past year was presented and the Sectionremains in sound financial shape. No fiscal concerns wereraised. The Tumor Section/AACR conference in San Diego(June 7-11, 1997) had a deficit of $26,843. The Tumor Sectionagreed to cover half of this deficit ($13,400).

Awards CommitteeAward winners at the 1998 CNS Annual Meeting were:

Preuss Award Bob Carter, MDYoung Investigator Award Eric Elowitz, MDMahaley Award Byron Young, MD

A standardized format for awards management was preparedby Dr. Black and adopted. The suggestion was made to includea check box on abstract forms to denote whether the author is aresident or practicing neurosurgeon. This will help determineappropriate candidates for awards.

Bylaws CommitteeDr. Rock has finished his work on the bylaw revision. A

quorum of five members is required for business and the finalcopy will be mailed soon. The bylaws revision has been ap-proved by the AANS Executive Committee and is pendingreview by the CNS Executive Committee. Final approvalshould be obtained by February 1999.

Education CommitteeDr. Couldwell has completed his listing of fellowships in

neuro-oncology, which will be published in the Journal of Neuro-Oncology. He will now begin a project to outline requirementsfor residency training and medical schools. Dr. Laws, speakingas a representative of the RRC, added that the RRC is reviewingfellowships to provide accreditation without certification.

Requirements will include that the fellowships must be servedafter completing a residency and must have specific goals andobjectives as per the ACGME. Dr. Berger added those corecurricula for residents should be from the Executive Committeeand will be completed in collaboration with the Congress ofNeurological Surgeon’s Education Committee.

A final draft of the fellowship criteria in neuro-oncology is nowbeing completed and will be presented at the 1999 AANS AnnualMeeting. Dr. Couldwell and Vince Traynelis, MD, have pro-duced an initial draft of a resident curriculum for tumor-relatedneurosurgery. This project is a joint effort between the AANS/CNS Section on Tumors and CNS Education Committee.

Membership CommitteeDr. McDermott sent 112 letters to program directors recruit-

ing new members. He received 31 new applications, 14 of whichcame from the Satellite Symposium in Philadelphia, Pennsylva-nia. The current membership is near 660 and Dr. McDermottwill continue to pursue membership recruitment.

Membership Services CommitteeDr. Asher has completed a formidable task of adding services

in collaboration with the official Web site of the AANS andCNS — NEUROSURGERY://ON-CALL®. These includetumor-related publications, fellowship listings, research supportand grant opportunities, meetings/educational resources,negative trial survey, support services for the N://OC® PublicPages, national cancer database, and a select review in neuro-oncology. The latter project will encompass the use of 30reviewers from all the related disciplines to provide reviews ofrelated publications. This will be updated quarterly and willrequire users to download Acrobat Reader off of N://OC®.

Program CommitteeDr. Rock reported that CNS Annual Meeting speakers have

been confirmed. Dr. Warnick will serve as Program Chair forthe 1999 AANS meeting. He plans a symposium on intraopera-tive MRI to include six talks on concepts, applications, use andcase summary. Dr. McDermott will plan the CNS program for1999 at the Program Committee meeting.

Research CommitteeDr. Glick provided information on grant writing and a list of

funding opportunities. It was clarified that Dr. Bullard can assistwith the RTOG as a source of funding if your hospital is aRTOG member.

Guidelines CommitteeDr. Rock updated the Metastasis Guideline. The literature

search has been conducted and the goal is to complete theproject by summer 1999. A similar project was announced by

Minutes of the Executive Council MeetingJoseph M. Piepmeier, MD

TUMOR SECTION NEWSLETTER n Spring 1999 11

the National Cancer Cooperative Network, which includes 15centers trying to establish guidelines for cancer managementfrom evidence-based data. This will be published in Oncology.

The literature review has been finalized and we will bemeeting during the AANS Annual Meeting to screen theliterature and determine the key articles which will serve asthe foundation for the Treatment of a Single Brain Metastasisin an Adult Guideline. All the work to date has been handledvia the Internet. The initial literature review is comprised of75 articles. Stephen Haines, MD, and Beverly Walters, MD,will facilitate the upcoming review meeting. Other teammembers include Jack Rock, MD (neurosurgery), MarkBernstein, MD (neurosurgery), Raymond Sayawa, MD(neurosurgery), Tom Mikkelsen, MD (neuro-oncology),Larry Recht, MD (neuro-oncology), and Jay Loeffler, MD(radiation oncology). It is anticipated that the Guidelines willbe complete by October 1999.

Other Business

1998 Satellite SymposiumDr. Rutka reported financial data from the symposium of the

1998 AANS Annual Meeting. The Section generated over$9,000 in profit. Discussion was held regarding the nextSatellite Symposium. The 1999 CNS meeting in Boston willconflict with the next Society for Neuro-Oncology meeting;therefore, the next likely Symposium will be held at the 2000AANS meeting, but further plans will need to be explored. Ideasfor new practical courses were requested. The Devices andRadiation Health Panel of the FDA has requested a representa-tive, and Dr. Sekhar will step forward for our discipline.

Skull Base SectionDr. Sekhar presented reasons for a new Skull Base Section: 1)

Surgery encompasses several different pathologies, 2) Educa-tion and scientific needs, and 3) Encroachment upon skull basesurgery by ENT. Tom Origitano, MD, was invited to participatein the discussion. The suggestion was made to form an ad hoccommittee to evaluate ways to meet the needs of skull basesurgeons within the existing section.

Journal of Neuro-oncologyDr. Piepmeier will become the new Editor of the Journal of

Neuro-Oncology. It also was decided that when Kluwer deter-mines a reduced subscription rate for Tumor Section members,a subscription box would be added as an optional line item onthe membership statement.

American College of Surgeons Oncology GroupAs the American College of Surgeons Oncology Group Chair

for Neurosurgery, Dr. Laws solicited new ideas for clinical trials.

Tumor Section Makes Plans for 1999CNS Annual Meeting

The plans for the 1999 CNS Annual Meeting in Boston, Massa-chusetts are well underway. Following is a glimpse at the TumorSection’s Scientific Program planned for this year’s meeting.

Monday, November 1, 1999Spinal Cord NeoplasmsModerators: Joseph Piepmeier, MD; Michael McDermott, MD

2–2:25 PM Pathology of Intramedullary TumorsFaculty: Catherine Daumas–Duport, MD

2:25–2:50 PM Adjuvant Therapies for Spinal CordTumors

Faculty: Paul McCormick, MD

3:30–4 PM Oral PostersModerators: Ronald Warnick, MD; Anthony Asher, MD

3:30–4 PM Coffee Break with Exhibitors

4–5:30 PM Open PapersModerators: William Couldwell, MD, PhD; Roberta

Glick, MD

Preuss AwardYoung Investigator Award

Tuesday, November 2, 1999Issues in Skull Base SurgeryModerators: Ossama Al-Mefty, MD; Thomas Origitano, MD, PhD

2–2:20 PM Update on the Biology of Meningiomasand Implications for Non-OperativeTreatment

Faculty: Randy Jensen, MD

2:20–2:40 PM Cranial Base Surgery for MalignantTumors: When and When Not to Operate

Faculty: Franco De Monte, MD, FACS

2:40–2:50 PM Oral PostersModerators: James Markert, MD;

Michael McDermott, MD

3:30–4 PM Coffee Break with Exhibitors

4–5:30 PM Open PapersModerators: Raymond Sawaya, MD; James Rutka, MD

Mahaley Award

GO ProjectThe GO project is currently accumulating data from brain

tumor patients and hopefully will have some conclusions soon.

The meeting was adjourned at 8 AM.

12 Spring 1999 n TUMOR SECTION NEWSLETTER

760 Use of Intraoperative Ultrasound to Control theExtent of Tumor Resection in SupratentorialGliomas: Comparison With Postoperative MRIand Histopathological Findings Michael Woydt, A.Horowski, A. Krone, G. Becker, E. Hoffman, K.Roosen (Discussant: Richard Bucholz)

765 Extent of Tumor Resection and Survival ofPatients With Glioma Michael Lacroix, Dima Abi-Said, Weiming Shi, Franco DeMonte, Ziya Gokaslan,Frederick Lang, Ian McCutcheon, SamuelHassenbusch, Raymond Sawaya (Discussant: TBD)

772 Growth Regulated Oncogene in Oligodendroglio-mas: Constitutive Activation of a ProliferativePathway Shenandoah Robinson, J. Levine, M. Cohen,Robert H. Miller, (Discussant: Mitchel Berger)

774 Depression is an Under Treated Complication inPatients With High Grade Glioma: PreliminaryResults of the Glioma Outcomes Project N. ScottLitofsky, Frederick Anderson, Edward R. Laws, Jr., andthe Glioma Outcomes Project Investigators (Discus-sant: Griffith R. Harsh IV)

Thursday, April 29, 1999 Breakfast Seminars 6:45–9:30 AM

405 Treatment Options for Primary and RecurrentArachnoid Cysts

Moderator: Marion WalkerPanelists: David Jimenez, Dale Swift, Kiyoshi Sato

416 Advanced Techniques in the Treatment ofPituitary Tumors

Moderator: Edward R. Laws, Jr.Panelists: Kalmon Post, Alex Landolt, Gail Rosseau

Genetic Markers Classify Anaplastic Astrocytomas IntoPrognostic Groups and Explain Age-related SurvivalSandeep Kunwar, Gayatry Mohapatra, Michael Prados, BurtFeuerstein

Objectives: Anaplastic astrocytomas (AAs) have thepotential for further malignant progression and have age-dependent survival. To improve prognostic assessment and betterunderstand tumor behavior, we used comparative genomichybridization (CGH) to search for genotypic groups among AAsand examined their association with clinical parameters.

Methods: CGH was performed on 35 histologicallyconfirmed AAs. The ratio of FITC(green)-labeled tumor versusTR(red)-labeled normal DNA hybridized to normal metaphasespreads was used to determine chromosomal gains and losses.Clinical data was obtained by chart review.

Results: Chromosomal aberrations were associatedwith age and survival. -4q,-10,+7p, +19 and +5p occurred moreoften in patients >45 yo, while >11p was detected in youngerpatients (p<0.05, Fisher exact test). +8q, +10p, -12q and -14qalso occurred within defined age groups. Tumors with +7p or+7q were associated with a shorter median survival, whiletumors with -4q had longer survival, independent of age(p<0.05, logrank exact test). Overall, patients with normal 7 hadsignificantly longer survival than patients with gains on 7 (5-year survival, 84 percent versus 16 percent respectively,p=0.002, logrank exact). +7p, +7q, +8q and -10 were associatedwith a shorter progression free survival, independent of age(p<0.05, longrank exact).

Conclusion: These results indicate that age influences thegenetic pathways in tumor development and that genetic markersbetter predict survival than current prognostic indicators. We willfurther discuss the clinical correlates of these observations incomparison to changes seen in glioblastoma patients.

Preuss Resident’s Research Award Paper

Meeting Highlights continued from page 3

St. Louis Cathedral is the country’s oldest active cathedral, located in theheart of the French Quarter, Jackson Square. Photo courtesy of NOMCVB.

TUMOR SECTION NEWSLETTER n Spring 1999 13

Stereotactic Radiosurgery Plus Whole Brain RadiotherapyVersus Whole Brain Radiotherapy Alone for Patients WithMultiple Brain Metastases: A Prospective, Randomized TrialDouglas Kondziolka, Atul Patel, L. Dade Lunsford, Amin Kassam,John C. Flickinger

Objective: Multiple brain metastases are a commonproblem with a poor prognosis. Radiosurgery is effective forpatients with solitary brain metastases that leads to long-termlocal tumor control and improved survival in case series. Wehypothesized that radiosurgery plus whole brain radiotherapy(WBRT) would provide a 40 percent improvement in localbrain tumor control over WBRT alone (the primary outcome)that would relate to improved survival in patients with 2-4brain metastases.

Methods: Patients with 2-4 tumors, all <25mm diam-eter and known primary tumor type, were randomized to initialcare with WBRT alone (30 Gy in 10 fractions) or WBRT plusradiosurgery. Extent of extracranial cancer, tumor diameter, andfunctional status were recorded.

Results: An interim analysis was performed at 2/3accrual. Twenty-seven patients were randomized (14 to WBRTalone and 13 to WBRT plus radiosurgery). The groups were

Mahaley Clinical Research Award Paper

well matched to age, sex, tumor type, number of tumors, andextent of extracranial disease. The rate of local failure at oneyear was 100 percent after WBRT alone but only 8 percent inpatients who had boost radiosurgery. The median time to localfailure was six months after WBRT alone (95 percent C.I., 3.5-8.5) in comparison to 36 months (95 percent C.I., 15.6-57) afterWBRT plus radiosurgery (p=0.0005). The median time to anybrain failure was improved in the radiosurgery group (p=0.002).Tumor control did not depend on histology (p=0.85), number ofinitial brain metastases (p=0.25), or extent of extracranialdisease (p=0.26). Patients in the initial WBRT alone group liveda median of 7.5 months, while those that received WBRT plusradiosurgery lived 11 months (p=0.22). However, since someWBRT alone patients had later radiosurgery for treatment oftumor progression, a survival difference was found betweenWBRT alone, and WBRT plus delayed radiosurgery, andWBRT plus initial radiosurgery (p=0.04). There was noneurologic or systemic morbidity related to radiosurgery.

Conclusion: Combined radiosurgery and whole brainradiotherapy for patients with two to four brain metastasessignificantly improves control of brain disease and this leads toa survival benefit. Whole brain radiotherapy alone does notprovide lasting and effective care for most patients.

Intraoperative Detection of Malignant Gliomas by5-ALA-induced Photoporphyrin-IX FluorescenceWalter Stummer, Susanne Stocker, Peter A. Winkler,Hans J. Reulen

Objective: Survival from malignant glioma is linked tothe completeness of tumor removal. Therefore, methods thatpermit intraoperative identification of residual tumor tissuemay be of benefit. To this purpose, we have studied the value offluorescent porphyrins, which are known to accumulate inmalignant tissue after administration of a precursor, 5-aminolaevulinic acid (5ALA), for labeling and enhancingresection of malignant glioma.

Methods: Thirty-seven patients with malignant gliomasreceived 20mg/kg 5-ALA orally three hours before anesthesia.Intraoperative fluorescence visualization was accomplished bya 455nm longpass filter integrated into the operating micro-scope and illumination with violet-blue (375-440nm) xenon-light. Biopsies were taken from the tumor border, based on the

presence or absence of fluorescence. Survival analysis wasperformed to assess the influence of histology, age, residualintraoperative fluorescence of residual enhancement in earlypost-operative MRI.

Results: Normal brain tissue revealed no porphyrinfluorescence whereas tumor tissue was easily distinguished bylucid red fluorescence. In 283 tissue biopsies, sensitivity was86.9 percent and specificity 100 percent. Falsely negativesamples contained gross necrosis (4 of 31 biopsies) or tumor oflow cellular density (21 of 31 biopsies). Survival was superior inyounger patients without residual intraoperative fluorescence,marginally superior in patients without residual enhancementon MRI, and superior in all patients operated on with 5-ALAcompared to a historic collective (n=89, 1990-1992).

Conclusion: Our observations suggest that 5-ALA-inducedporphyrin fluorescence labels malignant glioma accurately enoughfor more complete tumor removal, thus prolonging survival,especially if residual fluorescence is removed completely.

Young Investigator Award Paper

AANS/CNS Section on Tumors22 South Washington StreetPark Ridge, Illinois 60068-4287

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ChairmanMark Bernstein, MD

Past-ChairmanWilliam Chandler, MD

Secretary-TreasurerJoseph Piepmeier, MD

Advisory BoardMitchel Berger, MDDennis Bullard, MDPaul Kornblith, MDTimothy Mapstone, MDRobert Morantz, MDRaymond Sawaya, MDLaligam Sekhar, MDMichael Walker, MD

Section on Tumors Officers

Committee ChairsAwardsPeter Black, MDEdward Laws, MD

BylawsJack Rock, MD

EducationWilliam Couldwell, MD

InternationalArmando Basso, MDNicholas de Tribolet, MDAndrew Kaye, MDKintomo Takakura, MDDavid Thomas, MD

MembershipMichael McDermott, MD

Membership ServicesAnthony Asher, MD

NewsletterRonald Warnick, MD

NominatingWilliam Chandler, MD

ProgramMichael McDermott, MDRonald Warnick, MD

ResearchRoberta Glick, MD

Task ForcesJack Rock, MDMark L. Rosenblum, MD

Young NeurosurgeonsNelson Oyesiku, MD